Mediating role of depression in linking rheumatoid arthritis to all-cause and cardiovascular-related mortality: A prospective cohort study

Objective: This study aimed to analyze the associations between rheumatoid arthritis (RA) and all-cause mortality and cardiovascular disease (CVD)-related mortality using data from the National Health and Nutrition Examination Survey (NHANES) and examine the potential mediating role of depression in these correlations. Methods: 19,165 participants across five NHANES cycles from 2007 to 2016 participated in this study. Multifactorial Cox regression models between RA, depression and two mortality outcomes and multifactorial regression models between RA and depression were constructed to examine their associations. The mediating role of depression has also been investigated. Results: The prevalence of RA in this study was 6.57 %, the all-cause mortality of RA patients was 20.57 %, and the CVD-related mortality was 6.12 %. In the fully adjusted model, RA was associated with all-cause mortality [hazard ratio (HR) = 1.28, 95 % confidence interval (CI) = 1.12 to 1.48] and CVD-related mortality (HR = 1.33, 95 % CI = 1.03 to 1.72), without detectable interaction among subgroups (P for interaction >0.05). RA also had a positive correlation with depression. Depression score demonstrated pronounced mediating effects in the connections between RA and two types of mortality, with mediation ratios of 18.2 % and 18.9 %. Limitations: The diagnosis of RA is self-reported and may be subject to recall bias. Conclusions: RA was positively correlated with the risk of all-cause mortality and CVD-related mortality. Depression partially mediates these associations. Close attention to and active improvement of mental health in RA patients will be critical to decrease all-cause mortality and CVD-related mortality.